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| 1 | Microbiota-host interactions in irritable bowel syndrome: Epithelial barrier, immune regulation and brain-gut interactions显示文摘Irritable bowel syndrome(IBS) is a common, sometimes debilitating, gastrointestinal disorder worldwide. While altered gut motility and sensation, as well as aberrant brain perception of visceral events, are thought to contribute to the genesis of symptoms in IBS, a search for an underlying aetiology has, to date, proven unsuccessful. Recently, attention has been focused on the microbiota as a possible factor in the pathogenesis of IBS. Prompted by a number of clinical observations, such as the recognition of the de novo development of IBS following enteric infections, as well as descriptions of changes in colonic bacterial populations in IBS and supported by clinical responses to interventions, such as antibiotics and probiotics, that modify the microbiota, various approaches have been taken to investigating the microbiota-host response in IBS, as well as in animal models thereof. From such studies a considerable body of evidence has accumulated to indicate the activation or upregulation of both factors involved in bacterial engagement with the host as well host defence mechanisms against bacteria. Alterations in gut barrier function, occurring in response, or in parallel, to changes in the microbiota, have also been widely described and can be seen to play a pivotal role in generating and sustaining host immune responses both within and beyond the gut. In this manner a plausible hypothesis, based on an altered microbiota and/or an aberrant host response, for the pathogenesis, of at least some instances of IBS, can be generated. | Niall P Hyland Eamonn MM Quigley Elizabeth Brint | 2014 | World Journal of Gastroenterology2014，20，27： | 22 |
| 2 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 3 | Metabolic syndrome does not affect sustained virologic response of direct-acting antivirals while hepatitis C clearance improves hemoglobin A1c显示文摘AIM To determine whether successful treatment with direc-tacting antivirals(DAA) is associated with improvements in hemoglobin A1 c(HbA1 c) and if type 2 diabetes mellitus(T2 DM) or metabolic syndrome affects sustained virologic response(SVR).METHODS We performed a retrospective analysis of all hepatitis C virus(HCV) patients at the VA Greater Los Angeles Healthcare System treated with varying DAA therapy between 2014-2016. Separate multivariable logistic regression was performed to determine predictors of HbA1 c decrease ≥ 0.5 after DAA treatment and predictors of SVR 12-wk post treatment(SVR12).RESULTS A total of 1068 patients were treated with DAA therapy between 2014-2016. The presence of T2 DM or metabolic syndrome did not adversely affect SVR12. 106 patients had both HCV and T2 DM. Within that cohort,patients who achieved SVR12 had lower mean HbA1 c pre treatment(7.35 vs 8.60,P = 0.02),and lower mean HbA1 c post-treatment compared to non-responders(6.55 vs 8.61,P = 0.01). The mean reduction in HbA1 c after treatment was greater for those who achieved SVR12 than for non-responders(0.79 vs 0.01,P = 0.03). In adjusted models,patients that achieved SVR12 were more likely to have a HbA1 c decrease of ≥ 0.5 than those that did not achieve SVR12(adjusted OR = 7.24,95%CI: 1.22-42.94). CONCLUSION In HCV patients with T2 DM,successful treatment with DAA was associated with a significant reduction in HbA1 c suggesting that DAA may have a role in improving insulin sensitivity. Furthermore,the presence of T2 DM or metabolic syndrome does not adversely affect SVR12 rates in patients treated with DAA. | Tien S Dong Elizabeth S Aby Jihane N Benhammou Jenna Kawamoto Steven-Huy Han Folasade P May Joseph R Pisegna | 2018 | World Journal of Hepatology2018，10，9： | 4 |
| 4 | Malnutrition negatively impacts the quality of life of patients with cirrhosis: An observational study显示文摘AIM To verify how malnutrition is related to health-related quality of life(HRQL) impairment in patients with cirrhosis.METHODS Data was retrospectively abstracted from medical records and obtained by direct interview. We included patients with cirrhosis from any etiology, evaluated at the Liver Clinic from Gastroenterology Department in a tertiary healthcare center, from June 2014 to June 2016. Child-Pugh score, data about complications, and demographic, clinical and anthropometric characteristics of patients were obtained. Nutritional status was evaluated by the Subjective Global Assessment(SGA). HRQL was evaluated through the Chronic Liver Disease Questionnaire. Patients were requested to assess their global HRQL with the following code: 0 = impairment of HRQL, when it was compared with other healthy subjects; 1 = good HRQL, if it was similar to the quality of life of other healthy subjects. To compare the primary outcome between malnourished and well-nourished groups, the χ~2 test, Fisher's exact test or Student's t-test were used, based on the variable type. Associations between predictor variables and deterioration of HRQL were determined by calculating the hazard ratio and 95% confidence interval using Cox proportional hazards regression. RESULTS A total of 127 patients with cirrhosis were included, and the mean age was 54.1 ± 12.3 years-old. According to Child-Pugh scoring, 25(19.7%) were classified as A(compensated), 76(59.8%) as B, and 26(20.5%) as C(B/C = decompensated). According to SGA, 58(45.7%) patients were classified as well-nourished. Sixty-nine patients identified HRQL as good, and 76 patients(59.8%) perceived impairment of their HRQL. Multivariate analysis to determine associations between predictor variables and self-perception of an impairment of HRQL found strong association with malnutrition(P < 0.0001). The most important impaired characteristics in malnourished patients were: Presence of body pain, dyspnea on exertion with daily activities, decreased appetite, generalized weakness, trouble lifting or carrying heavy objects, and decreased level of energy(P < 0.0001).CONCLUSION Malnutrition is a key factor related to impairment of HRQL in patients with cirrhosis. | Gabriela Rojas-Loureiro Alfredo Servín-Caamano Elizabeth Pérez-Reyes Luis Servín-Abad Fátima Higuerade la Tijera | 2017 | World Journal of Hepatology2017，9，5： | 3 |
| 5 | Reproducibility of the diagnosis of dysplasia in Barrett esophagus: A reaffirmation显示文摘 | Elizabeth Montgomery Mary P Bronner John R Goldblum Joel K Greenson Marian M Haber John Hart Laura W Lamps Gregory Y Lauwers Audrey J Lazenby David N Lewin Marie E Robert Alicia Y Toledano Yu Shyr Kay Washington | 2001 | Human Pathology2001，，4： | 3 |
| 6 | Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice显示文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications. | Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews | 2020 | World Journal of Gastroenterology2020，26，23： | 3 |
| 7 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 8 | Senescent human hepatocytes express a unique secretory phenotype and promote macrophage migration显示文摘AIM:To develop a model of stress-induced senescence to study the hepatocyte senescence associated secretory phenotype(SASP).METHODS:Hydrogen peroxide treatment was used to induce senescence in the human Hep G2 hepatocyte cell line.Senescence was confirmed by cytochemical staining for a panel of markers including Ki67,p21,heterochromatin protein 1β,and senescence-associated-β-galactosidase activity.Senescent hepatocytes were characterised by gene expression arrays and quantitative polymerase chain reaction(q PCR),and conditioned media was used in proteomic analyses,a human chemokine protein array,and cell migration assays to characterise the composition and function of the hepatocyte SASP.RESULTS:Senescent hepatocytes induced classical markers of senescence(p21,heterochromatin protein1β,and senescence-associated-β-galactosidase activity);and downregulated the proliferation marker,Ki67.Hepatocyte senescence induced a 4.6-fold increase in total secreted protein(P=0.06)without major alterations in the protein profile.Senescence-induced genes were identified by microarray(Benjamini Hochbergcorrected P<0.05);and,consistent with the increase in secreted protein,gene ontology analysis revealed a significant enrichment of secreted proteins among inducible genes.The hepatocyte SASP included characteristic factors such as interleukin(IL)-8 and IL-6,as well as novel components such as SAA4,IL-32and Fibrinogen,which were validated by q PCR and/or chemokine protein array.Senescent hepatocyteconditioned medium elicited migration of inflammatory(granulocyte-macrophage colony stimulating factor,GM-CSF-derived),but not non-inflammatory(CSF-1-derived)human macrophages(P=0.022),which could contribute to a pro-inflammatory microenvironment in vivo,or facilitate the clearance of senescent cells.CONCLUSION:Our novel model of hepatocyte senescence provides insights into mechanisms by which senescent hepatocytes may promote chronic liver disease pathogenesis. | Katharine M Irvine Richard Skoien Nilesh J Bokil Michelle Melino Gethin P Thomas Dorothy Loo Brian Gabrielli Michelle M Hill Matthew J Sweet Andrew D Clouston Elizabeth E Powell | 2014 | World Journal of Gastroenterology2014，20，47： | 2 |
| 9 | Metabolite profile comparisons between ascending and descending colon tissue in healthy adults显示文摘BACKGROUND Obesity is a risk factor for colorectal cancer,yet metabolic distinctions between healthy right and left colon tissue,before cancer is diagnosed,remains largely unknown.This study compared right-ascending and left-descending colon tissue metabolomes to identify differences from the stool metabolome in normal weight,overweight,and obese adults.AIM To examine right and left colon tissue metabolites according to body mass index that may serve as mechanistic targets for interventions and biomarkers for colon cancer risk.METHODS Global,non-targeted metabolomics was applied to assess right-ascending and left-descending colon tissue collected from healthy adults undergoing screening colonoscopies to test the hypothesis that BMI differentially impacts colon tissue metabolite profiles.The colon tissue and stool metabolome of healthy adults(n=24)was analyzed for metabolite signatures and metabolic pathway networks implicated in progression of colorectal cancer.RESULTS Ascending and descending colon contained 504 host,food,and microbiotaderived metabolites from normal weight,overweight and obese adults grouped according to body mass index.Amino acids,lipids,and nucleotides were among the chemical types that further differentiated from the stool metabolite profiles.Normal weight adults had 46 significantly different metabolites between ascending and descending colon tissue locations,whereas there were 37 metabolite differences in overweight and 28 metabolite differences for obese adults(P<0.05).Obese adults had trimethylamine N-oxide,endocannabinoids and monoacylglycerols with different relative abundances identified between ascending and descending colon.Primary and secondary bile acids,vitamins,and fatty acids also showed marked relative abundance differences in colon tissue from overweight/obese adults.CONCLUSION There were metabolite profile differences between right-ascending and leftdescending colon tissue in healthy adults.Colon lipids and other metabolites in obese and overweight adults were distinguished from normal weight participants and associated with gut inflammation,nutrient absorption,and products of microbiota metabolism. | Bridget A Baxter Kristopher D Parker Michael J Nosler Sangeeta Rao Rebecca Craig Catherine Seiler Elizabeth P Ryan | 2020 | World Journal of Gastroenterology2020，26，3： | 2 |
| 10 | Evidence That the Diabetes Gene Encodes the Leptin Receptor: Identification of a Mutation in the Leptin Receptor Gene in db / db Mice显示文摘 | Hong Chen Olga Charlat Louis A Tartaglia Elizabeth A Woolf Xun Weng Stephen J Ellis Nathan D Lakey Janice Culpepper Karen J More Roger E Breitbart Geoffrey M Duyk Robert I Tepper Jay P Morgenstern | 1996 | Cell1996，，3： | 2 |
| 11 | Global prevalence of dementia: a Delphi consensus study显示文摘 | Cleusa P Ferri Martin Prince Carol Brayne Henry Brodaty Laura Fratiglioni Mary Ganguli Kathleen Hall Kazuo Hasegawa Hugh Hendrie Yueqin Huang Anthony Jorm Colin Mathers Paulo R Menezes Elizabeth Rimmer Marcia Scazufca | 2005 | The Lancet2005，，9503： | 2 |
| 12 | Global prevalence of dementia: a Delphi consensus study显示文摘 | Cleusa P Ferri Martin Prince Carol Brayne Henry Brodaty Laura Fratiglioni Mary Ganguli Kathleen Hall Kazuo Hasegawa Hugh Hendrie Yueqin Huang Anthony Jorm Colin Mathers Paulo R Menezes Elizabeth Rimmer Marcia Scazufca | 2005 | The Lancet . 2005 (9503)2005，，9503： | 2 |
| 13 | An attempt to close the daytime surface energy 显示文摘 | Matthias M Raymond L D Elizabeth P | 2010 | Boundary-Layer Meteorology2010，136，2： | 1 |
| 14 | Aluminum accumulationand its relationship with mineral plant nutrients in 12 pteridophytesfrom Venezuela 显示文摘 | Elizabeth O Eder P Eunice M | 2009 | Environ Exp Bot2009，65，13： | 1 |
| 15 | Downey显示文摘 | Albert W Small P D Elizabeth A | 2001 | Managing Change: Some Important Aspects2001，，10： | 1 |
| 16 | Evolution of Developmental Diversity Meeting: RNAi Takes Evo-Devo World by Storm显示文摘 | Elizabeth P | 2004 | Science2004，304，： | 1 |
| 17 | The prognostic value of histology in the assessment of patients with Budd–Chiari syndrome显示文摘 | Thjon J Tang Kenneth P Batts Piet C de Groen Bart van Hoek Elizabeth B Haagsma Wim C.J Hop Harry L.A Janssen | 2001 | Journal of Hepatology2001，，3： | 1 |
| 18 | New media conerage go smoking and health is associated with changes in population rates of smoking cessation but not imitation显示文摘 | JOHN P ELIZABETH A G | 2001 | Tob Control2001，10，2： | 1 |
| 19 | The Receptor for Urokinase-type Fibroblasts显示文摘 | ELIZABETH M VERTMAN G CARBON W P | 2004 | J Biol Chem2004，279，2： | 1 |
| 20 | On computer simulation methods to model Zener pinning 显示文摘 | Azmir Harun Elizabeth A Holm Mike P Clode | | Aeta Mater0，，： | 1 |
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